"Chemoembolization", the intraarterial delivery of chemotherapeutic agents in particulate form is a procedure which has recently been used both experimentally and in clinical practice: e.g., Kato et al. (1981), A 245 (11): 1123-1127; and Soo and Wallace (1982), diovasc. Intervent. Radiol. 5: 260-263. For this purpose, microspheres in the approximate size range of 50-300 microns are advantageous. The microspheres are introduced as a slurry into an artery supplying neoplasmic aggregate in the peripheral branches, and form a temporary or permanent blockage of the blood flow. The chemotherapeutic agent is thereby concentrated at the desired site. The release rate may be controlled by the character of the matrix material.
The methods for forming microspheres of below 5 microns in size, i.e. 0.5 to 1 micron, is presented; heretofore there has not been a commercially satisfactory procedure for conveniently and consistently producing microspheres in this size range for intravenous delivery. Such a process is especially needed for the controlled, prolonged release of almost any pharmaceutic agent. By concentrating the drug release at the site of the tumor, the effectiveness of the drug can be greatly enhanced while minimizing the undesirable side effects.
The patent art relating to the preparation of liquid-center microspheres, particularly by the technique of coacervation, is voluminous. The patent art of entrapment encapsulation is much less extensive. Further, no patent or other prior art directly relevant to the method of this invention is known. However, the following patents are believed to be illustrative of the general art of entrapment encapsulation to produce solid microspheres.